Macrophage Accumulation, Division, Maturation and Digestive and Microbicidal Capacities in Tuberculous Lesions: I. Studies Involving their Incorporation of Tritiated Thymidine and their Content of Lysosomal Enzymes and Bacilli

Dermal and pulmonary tuberculous lesions were produced in rabbits with BCG, biopsied, incubated in vitro with tritiated thymidine (³HT) under hyperbaric oxygen, quickly frozen, sectioned in a cryostat, stained for the lysosomal enzyme β-galactosidase, autoradiographed, stained for acid-fast bacilli and counterstained with hematoxylin. As macrophages developed into epithelioid cells, they could still divide—ie, incorporate ³HT. However, once they became fully mature epithelioid cells that were 4-plus in β-galactosidase, they could not do so. Tuberclebacilli did not stimulate macrophage division. On the contrary, macrophages containing bacilli did not divide, except when the lesions began. During the development of tuberculous lesions, macrophages (including those rich in enzymes and those containing bacilli) died, forming caseous centers. Therefore, local cell division did not seem to be the main mechanism by which macrophages reduced their bacillary load. Such division seemed mainly to occur in young macrophages that had recently immigrated into the lesions from the bloodstream and had not yet ingested bacilli.     

Mycobacterium-induced potentiation of type 1 immune responses and protection against malaria are host specific

Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long- and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-gamma) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-gamma responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria.     

Effects of dexamethasone and transient malnutrition on rabbits infected with aerosolized Mycobacterium tuberculosis CDC1551

Malnutrition is common in the developing world, where tuberculosis is often endemic. Rabbits infected with aerosolized Mycobacterium tuberculosis that subsequently became inadvertently and transiently malnourished had compromised cell-mediated immunity comparable to that of the rabbits immunosuppressed with dexamethasone. They had significant leukopenia and reduced delayed-type hypersensitivity responses. Malnutrition dampened cell-mediated immunity and would interfere with diagnostic tests that rely on intact CD4 T-cell responses.     

Cribriform-morular variant of papillary carcinoma: the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma. A case report with clinical and molecular genetic correlation

The increased incidence of thyroid carcinomas in familial adenomatous polyposis (FAP) patients is well recognised. These thyroid neoplasms display distinctive clinicopathological features and generally show good prognostic outcome. Recently, unusual sporadic tumours that share the morphological features of FAP-associated thyroid carcinomas have also been described. In this report, we document a case of a thyroid tumour in a previously well, 46-year-old female. Histology revealed a circumscribed neoplasm composed of tubular, papillary, cribriform and solid areas. The pseudostratified columnar tumour cells showed occasional nuclear grooves and rare nuclear inclusions. Immunohistochemistry showed positive staining with antibodies to cytokeratin AE1/AE3, oestrogen and progesterone receptor proteins. Focal immunoreactivity was also noted with antibodies to thyroglobulin, epithelial membrane antigen, 34betaE12 and cytokeratin CK7. The absence of polyps on colonoscopy and germline mutation in the adenomatous polyposis coli (APC) gene provides evidence that this tumour represents the sporadic counterpart of FAP-associated thyroid carcinoma. The patient is well with no evidence of disease 7 months following resection of the tumour. The differential diagnoses and molecular genetics of this unusual tumour are discussed.     

The efficacy of montelukast in the treatment of cat allergen-induced asthma in children

BACKGROUND: Montelukast is a leukotriene antagonist approved for the treatment of childhood asthma in children age 2 years and older. There are limited studies on its effects on allergic asthma in children. OBJECTIVE: We sought to evaluate montelukast's effects on upper and lower airway responses to intense cat allergen exposure. METHODS: In a double-blind, placebo-controlled, cross-over trial 18 subjects aged 6 to 14 years with cat-induced asthma were randomly assigned to receive 1 week each of either montelukast or placebo, followed by a 1-hour cat challenge in an environmental exposure unit. Upper and lower respiratory tract symptoms were rated, and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject became too uncomfortable or had a greater than 50% decrease in FEV1. RESULTS: Overall changes in FEV1 were significantly different with montelukast treatment and remained significant after adjusting for allergen level (P =.02; adjusted P =.01). Lower respiratory tract symptom scores were significantly reduced with montelukast versus placebo (P =.007) but lost significance after adjusting for allergen level (P =.16). Challenge length was significantly longer with montelukast versus placebo (P <.001) and remained significant after adjusting for allergen level (P =.019). Montelukast did not significantly affect upper respiratory responses, as measured by means of symptom scores (P =.43) and changes in acoustic rhinometry (P =.078). CONCLUSIONS: Montelukast was significantly more effective than placebo in attenuating lower respiratory responses and extending challenge length when cat-sensitive children with mild persistent asthma were exposed to high levels of cat allergen.     

Ultrasonic evaluation of retinoblastoma

Seventeen children presenting with leucocoria were subjected to complete investigations. Careful A and B mode ultrasonography allowed us to make the correct diagnosis of retinoblastoma in 11 eyes of 9 patients, which was confirmed by histopathology or by response to radiotherapy. The diagnosis of retinoblastoma was not missed ultrasonographically in any of the eyes studied. The "V/W" configuration and absence of vascular pulsations on A mode; the "mixed" pattern and absence of choroidal excavation and orbital shadowing on B mode were found to be essential echographic features in characterizing the tumor and in differentiating it from other conditions including vitreous hemorrhage. The ultrasonographic features of early extraocular extension of retinoblastoma are discussed. Careful ultrasonic evaluation of leucocoria would seem to be invaluable in obviating the possibility of misdiagnosis in such problematic cases.     

Caffeine protects mice against whole-body lethal dose of gamma-irradiation.

Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of gamma-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the oxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice.     

Cervical cancer screening in Tamilnadu, India: a feasibility study of training the village health nurse

Uterine cervical cancer is the most common malignancy among females in developing countries, including India. The success of cervical cancer screening programs in North America and Western Europe has been the result of centralized cervical-cytology screening. This is not possible in the villages (n=17,000) of Tamilnadu where 58 percent of females in rural areas are illiterate, health infrastructure is mediocre, and cervical cytology is unknow. The present study was undertaken to examine if the village health nurse (VHN) could be trained quickly to identify a cervical abnormality by visual inspection so that we could down stage the cancer to earlier stages, more amenable to treatment. VHNs also would be trained to take an adequate Pap smear. A total of 101 VHNs were trained in batches and returned to their villages. Within two years, 6,459 engible women in the study area were screened. The agreement between the gynecologists and the VHNs in identifying cancer among those with abnormal cervix was 95 percent, and 80 percent of the Pap smears taken by VHNs were adequate by WHO criteria, making the feasibility study highly successful.Authors are with The Cancer Institute (WIA), Adyar, Madras, Tamil Nadu,India. Address correspondence to Dr Gajalakshmi, Epidemiology Division and Cancer Registry, 18, Sardar Patel Road, Cancer Institute (WIA), Madras-600 036, Tamilnadu, India. This project was funded by the Indian Council of Medical Research, Government of India, New Delhi, India.520 Cancer Causes and Control. Vol 7. 1996